Twin and adoption studies suggest that 30-60% of the variance in most personality traits is due to inherited factors. However, there is little knowledge of the number or identity of the responsible genes, how they differ between individuals, or how their gene products interact with the developing brain and with environmental and experiential factors to generate the complex blend of attitudes and actions that comprise human temperament. This project uses several validated personality inventories and measures of life events, present mood states and cognitive functions together with DNA obtained from blood or buccal swabs for genotyping. In a project completed this year, anxiety-related personality features from three personality inventories were found to be associated with the presence of the deletion form of a common insertion/deletion polymorphism in the promoter region of the serotonin transporter in two populations comprising 505 individuals. A within-pedigrees examination using sib-pairs discordant for the genotypes demonstrated that the association was genetically-based rather than a result of population stratification. Considerable prior evidence indicates that increased serotonergic neurotransmission (which would be an evident consequence of the reduced serotonin uptake capacity found in individuals with the deletion form of the polymorphism) is anxiogenic in animal models as well as in humans.